The over-arching objectives of the Neuromedical Core (NMC) are to provide comprehensive clinical and laboratory evaluations, scientific consultation, and mentorship, training, and community education in NeuroAIDS. In the current funding period the NMC facilitated 79 research projects including observational cohort studies, clinical-pathological investigations, imaging studies, clinical trials and international research performed by collaborating investigators at UCSD and many other institutions. The HNRC's collaborating investigators find data generated by the NMC, including neurological diagnostic formulations, antiretroviral (ARV) treatment information, HIV disease staging information, viral loads and a variety of other clinical laboratory measurements, to be essential for their data analyses and publications. Recognizing that maintaining vitality and scientific relevance necessitates continual adaptation to the changing needs of the HNRC research enterprise and the scientific agendas of its many principal investigators and collaborators, we propose to enhance the NMC in this renewal in two ways. First, we will add a pharmacology component that will focus on ARV drug penetration into the CMS. Second, we will incorporate functions previously carried out by the Cellular Immunology and Fluids Core. The newly-organized NMC is made up of three cooperative units, each comprising common resources (equipment, supplies) and staff that interact on a daily basis: a Clinical Unit;a Patient-Derived Sample Unit;and a Pharmacology &Biomarker Unit. Examples of scientific questions the Core will facilitate answering are 1) What is the contributory role in neuroAIDS of co-pathogens and comorbidities such as hepatitis C virus (HCV) and substance abuse? 2) Does cerebrospinal fluid (CSF) provide a useful window to evaluate virus-host interactions and molecular pathogenesis in neuroAIDS? 3) What is the role of the CNS in viral evolution, adaptation and the occurrence of ARV drug resistance? 4) How do host genetics influence HIV neuropathogenesis? By assisting investigators in widely diverging disciplines at all levels of project development, from conceptualization of hypotheses to study implementation, analysis, interpretation and dissemination, the NMC encourages the application of multiple scientific perspectives and stimulates interdisciplinary collaboration and coordination. We will collaborate closely with the Neuroimaging, Neurobehavioral, Neurovirology and Neurobiology Cores to further stimulate transdisciplinary aims. In addition to supporting the performance of research research, the NMC also enhances and extends the effectiveness and public health impact of new findings related to mental health and HIV/AIDS.